1. Field of the Invention
This invention provides a method of preparing a heterocyclic carbon compound containing, as the sole ring heteroatom, a nitrogen atom attached to two benzene rings. More specifically, the invention provides a method of preparing a 5H-dibenz[b,f]azepine-5-carboxamide.
2. Description of Related Art
10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (oxcarbazepine) is used to control some types of seizures in the treatment of epilepsy (Ziao, K., Reiner, J., and Xie, W., Frontiers of Biotechnology & Pharmaceuticals, 2:331-332). A number of methods to synthesize oxcarbazepine are known. For example, U.S. Pat. No. 5,808,058 (the '058 patent) discloses the following reaction scheme for the preparation of oxcarbazepine:

In this process, oxcarbazepine (III) is prepared by direct carbamoylation with isocyanic acid generated in situ from an alkali or alkaline-earth metal cyanate and a mineral or carboxylic acid, followed by acid hydrolysis of the enol ether (II). In each working example, the carbamoylation reaction was conducted at a temperature of ≧40° C., and took at least 4-24 hours.
The concentrated acid reagents employed in the method of the '058 patent are caustic and must be handled with extreme care. Moreover, many of the suggested acids, such as trichloroacetic acid, are costly.
According to EP 1 302 464 A1 (the '464 application), another drawback of the carbamoylation reaction disclosed in the '058 patent is that it creates a number of byproducts that make it difficult to purify the prepared oxcarbazepine. The '464 application attempts to solve that problem by replacing the mineral acid or carboxylic acid of the '058 patent with an aromatic carboxylic acid, such as benzoic acid. However, each example in the '464 application was performed at a temperature of at least 85° C., and reported yields were only 28% to 49%.
A need exists for a method of preparing a 5H-dibenz[b,f]azepine-5-carboxamide from safe, inexpensive, easy to handle reagents, wherein the reaction proceeds in high yield without producing byproducts that are difficult to separate.